Translational Approaches to the Neurobiological Study of Conditional Discrimination and Inhibition: Implications for Psychiatric Disease

There is a growing number of studies investigating discriminatory fear conditioning and conditioned inhibition of fear to assess safety learning, in addition to extinction of cued fear. Despite all of these paradigms resulting in a reduction in fear expression, there are nuanced differences among them, which could be mediated through distinct behavioral and neural mechanisms. These differences could impact how we approach potential treatment options in clinical disorders with dysregulated fear responses. The objective of this review is to give an overview of the conditional discrimination and inhibition findings reported in both animal models and human neuropsychiatric disorders. Both behavioral and neural findings are reviewed among human and rodent studies that include conditional fear discrimination via conditional stimuli with and without reinforcement (CS+ vs. CS−, respectively) and/or conditional inhibition of fear through assessment of the fear response to a compound CS−/CS+ cue versus CS+. There are several parallels across species in behavioral fear expression as well as neural circuits promoting fear reduction in response to a CS− and/or CS−/CS+ compound cue. Continued and increased efforts to compare similar behavioral fear inhibition paradigms across species are needed to make breakthrough advances in our understanding and treatment approaches to individuals with fear disorders.